FDA approves the first oral PCSK9 inhibitor tablet for high cholesterol treatment

Patients with hard-to-control high cholesterol may soon have the option of taking an oral medication as an alternative to potent injectable agents for lowering cholesterol, as the U.S. Food and Drug Administration (FDA) has approved the world's first oral PCSK9 inhibitor.

New Drug and Its Application

A daily tablet called Lipfendra (enlicitide) has received approval for adults with elevated cholesterol, including individuals with a hereditary condition known as heterozygous familial hypercholesterolemia (HeFH). The use of this drug should be combined with maintaining a diet, exercising, and current cholesterol-lowering treatment. Previously, PCSK9 inhibitors were available exclusively in injectable forms administered every two or four weeks.

Availability Situation in India

However, it is expected that this drug will not be immediately available in India. As noted by Dr. Subhash Mandal, National General Secretary of the Indian Pharmaceutical Association (IPA), even after overseas approval, the marketing of the drug in India does not happen automatically. In addition to patent restrictions, it must go through the approval process via CDSCO, which may include clinical trials according to Indian regulatory requirements. In exceptional cases, patients may request permission through a separate CDSCO mechanism to import limited quantities for personal use, but drugs cannot simply be brought into the country through friends or relatives.

Significance of Cholesterol Control

This approval is significant because many high-risk patients continue to have elevated levels of low-density lipoprotein (LDL) cholesterol despite taking standard oral medications. According to Indian cardiology guidelines, aggressive reduction of LDL levels is required: target levels are below 70 mg/dL for high-risk individuals and below 55 mg/dL for those in the very high cardiovascular risk group, but many patients do not reach these goals using multiple types of therapy.

Clinical Trial Results

Since cardiovascular diseases remain the leading cause of death in India, cardiologists emphasize that better control of LDL levels is key to preventing heart attacks and strokes. Clinical trials involving 3207 adults showed that this once-daily oral drug reduced LDL cholesterol by 56–59% over 24 weeks in patients who were already on maximally tolerated statins. The achieved reductions are comparable to those observed with injectable PCSK9 inhibitors, offering an additional option for those whose cholesterol remains uncontrolled despite existing therapy.

Limitations and Prospects of Use

Cardiologists warn that this drug is unlikely to replace statins or become a first-line treatment. Dr. Ambuj Roy, Professor of Cardiology at AIIMS Delhi, noted that PCSK9 inhibitors were previously only available as injections every two or four weeks. The new oral therapy reduces LDL, or 'bad' cholesterol, by approximately 50–60%, making it a promising option for patients who prefer to avoid injections. He suggested that the drug will likely be used as fourth-line therapy, after the use of statins, ezetimibe, and bempedoic acid, for patients whose LDL remains uncontrolled or who are intolerant to statins. Furthermore, he added that there is no long-term evidence that the drug reduces the incidence of heart attacks, aortic surgeries, stenting, or mortality, and it is expected to be expensive.